We are studying the changes in the regulation of breathing during exposure to high altitude or hypoxia in order to understand more fully the nature of mechanisms fundamental to control of breathing under all circumstances. Currently, our primary attention is focused on the mechanisms that control the bicarbonate and hence pH in the neighborhood of the medullary chemoreceptors. One factor we are studying here is the change in the electrical potential across the blood-brain barrier in chronic hypoxia. Another approach attempts to analyze brain extracellular fluid bicarbonate and pH by sampling from hollow capsules implanted in the brain. These studies arise from our concern with the disequilibrium of bicarbonate across the blood-brain barrier and our suspicion that brain extracellular fluid may not always resemble cerebrospinal fluid as closely as has been thought.